This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The hemocyanins are copper-containing respiratory proteins often present as large molecular assemblies in the hemolymph of many mollusks and arthropods. Besides the function of transporting oxygen, hemocyanin can be an effective immune-stimulant in mammals (including humans). For example, the hemocyanin of the giant keyhole limpet Megathura crenulata finds application as an immunotherapeutic agent for the treatment of certain cancers (Helling et al., 1994;Helling et al., 1995), and is used as diagnostic tool for bilharziosis and as a hapten carrier for AIDS vaccine (Naylor et al., 1991). Another perspective is that hemocyanins are involved in immune reaction to microbial challenge of mollusks and arthropods (Destoumieux-Garzon et al., 2001). A number of molluscan and arthropod hemocyanins are being investigated in terms of morphology, amino acid sequence, subunit composition, and structure. The subunit of molluscan hemocyanins is a polypeptide of ~400 kDa, folded into a series of seven or eight globular substructures, the so-called 'functional units'(FUs). Such a FU has a molecular mass of 45-65 kDa and carries a single binuclear copper active site. Allosteric regulation and cooperativity of hemocyanin subunits (as in arthropods) or FUs (as in mollusks) are responsible for the high oxygen affinity of the whole hemocyanin macromolecular assembly. Zhang's lab is interested in the structure properties of whole hemocyanin bound with hapten as an immune-stimulant. Difference maps of the apo-hemocyanin and hemocyanin-hapten complex would provide the location of such binding